“(−)-Nal” morphinan compounds, such as naltrexone, naloxone, nalmefene, and nalbuphine, are used in therapeutic applications as analgesics and antagonists. Recently, the (+)-nal morphinan enantiomers have been shown to have important bioactivities that differ from their (−) counterparts.
An important intermediate compound to produce a class of important (+)-opiates is (+)-dihydrothebaine. In particular, (+)-dihydrothebaine is an intermediate compound to make (+)-thebaine, which is a common intermediate to make a series of biologically active (+)-opiates, such as (+)-oxycodone, (+)-oxymorphone, (+)-naltrexone, (+)-naloxone, and (+)-nalbuphine. Traditionally, the synthesis of (+)-dihydrothebaine has required two steps: (1) synthesis of (+)-hydrocodone from dihydrosinomenine is prepared in a strong acid, and is then isolated and purified; and (2) pure (+)-hydrocodone is then converted to (+)-dihydrothebaine. This process, however, is time consuming because it requires the isolation of (+)-hydrocodone prior to its conversion to (+)-dihydrothebaine. Improved processes for the production of (+)-dihydrothebaine, and other intermediates used in the production of (+)-opiates are needed.